title: Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL.
abstract: CADASIL is an arteriopathy caused by mutations of the Notch3 gene. White matter hyperintensities (WMH), lacunar lesions (LL), cerebral microhemorrhages (CM), brain atrophy and tissue microstructural changes are detected on MRI. Using an integrated multi-modal approach, we examined the relative impact of lesion burden and location of these MRI markers on cognitive impairment and disability. Multi-modal imaging was performed on 147 patients from a two-center cohort study. Volume of LL, WMH and number of CM was determined. Whole brain mean apparent diffusion coefficient (mean-ADC) and brain parenchymal fraction (BPF) were measured. In multivariate models accounting for lesion burden and location, volume of LL, mean-ADC, and BPF each had an independent influence on global cognitive function and disability. BPF explained the largest portion of the variation in cognitive and disability scores (35-38%). Brain atrophy has the strongest independent influence on clinical impairment in CADASIL when all MRI markers in the disease are considered together. The results suggest that the clinical impact of cerebral tissue loss plays a principal role in this genetic model of subcortical ischemic vascular dementia.
authors.affiliation: Department of Neurology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Ophelia
authors.initials: O
authors.lastname: Godin
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.forename: Michael
authors.initials: M
authors.lastname: O'Sullivan
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Nils
authors.initials: N
authors.lastname: Peters
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guichard
authors.forename: Markus
authors.initials: M
authors.lastname: Holtmannspötter
authors.forename: Carole
authors.initials: C
authors.lastname: Dufouil
authors.forename: Chahin
authors.initials: C
authors.lastname: Pachai
authors.forename: Marie-Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D001921:Brain / Q000473:pathology*; D046589:CADASIL / Q000473:pathology*; D005260:Female; D005602:France; D005858:Germany; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity